Here is an article by Gallicano et al, which I think has some interesting ultrastructure. They created a desmoplakin ko, and followed some of the changes in structure, but I think there might be more changes than they allude to.  I took two of their micrographs and measured (using their own nm markers) the height of the wt desmosomal plaque, the extracellular space and the ring dimension of the annulus… and i think there is an effect of the lack of desmoplakin on how narrow the extracellular space is, and also there is an absence of the very electron lucent layer just above the plasmalemma of the desmosome (just immediately intracellular, almost one could say, beneath the plakophilin and plakoglobin). Since the position of both those proteins as well as the intracellular portion of desmocollin and desmoglein are linked directly and/or indirectly, then it would be reasonable to think that the extracellular dimension (as well as the intracellular thickness of the outer and inner plaques as well as the whole dimension of the desmosome might change.

Extracellular dimension of the ko desmosome, 19nm (according to their own micron marker), and the extracellular dimension for the wt desmosome is ,pre ;ole 16nm. In both the wt case, the extracellular space between those adjacent cells is wider than what is found actually at the desmosome.  This is not that apparent for the ko.   Similarly the annulus protein seems to be longer (wt=26nm ko=35nm)(though tangential section could easily account for this).  Just interesting to see how subtle changes in the TEM are present. Red and black vertical and horizontal bars=100nm. Green bar=extracellular space at desmosome. Pink bar=desmosomal annulus. Loss of IFs in image to the right, reflecting lack of desmoplakin connections with intermediate filaments, and I think too changing the position, orientation, and closeness of the four+ other proteins comprising the desmosome. (mouse).  Looking again at these micrographs, they are most assuredly NOT the same magnification as was indicated on their micrographs.

TOPIC: desmosomal diagrams

BACKGROUND: Desmosomes are cell-cell adhesion spots (not spot welds, but more like removable rivets, or bolts with phylanges, meshed with extracellular velcro-like (Ca dependent) intercellular hooks. Desmosomes are very specialized and highly ordered areas that incorporate many of these types of commercial connection devices. Velcro=desmocollins,desmogleins, double headed bolts or rivets=desmoplakin connectivity with the outer dense plaque proteins, and lock washers in particular the plakoglobin and plakophilin portions of the outer plaque proteins.  Desmosomes are commonly found in epithelialia, and I have seen them in particular right at the borders of the bile canaliculi in liver, at the apex of gut epithelial cells, and in kidney, and thyroid. I don’t think they are plentiful in lung, but I have not specifically searched for them there.  Of course desmosome-like junctions in heart, and muscle cells are unique adaptations of desmosomes. Others researchers have found them in thymus, cornea, and the central nervous system. Desmosomal protein isoforms and connections with filament proteins understandably are different in each cell type, and even with maturation state and location within the same tissue (e.g. different levels of epidermis). Electron microscopy (with electron tomography) remains the gold standard for studying desmosomes. Finding a good diagram of the desmosomal complex, identification of the desmosomal proteins and visual correlations with electron micrographs is not easy. HENCE the following post.

COMMENTS on one diagram:  I realize it is always risky to critique a diagram when on has not made a diagram for counter-critique. So please understand this is not a hostile critique, but a learning critique… it is the way I reinforce what is reasonable science and what is regarded generally as “fake data”  (ha ha… no deliberate reference to the current state of government and news reporting is made), it is instead an honest attempt to come up with something which is informative, and accurate.  The source of the diagram is irrelevant, since the purpose is to examine the content, not to criticize. I will just list the issues i have in bullet format.

1) the area marked dg, desmoglein, includes the plasmalemma from both adjacent cells…. this probably is not accurate, I would not have commented had the bracket stopped at the outer leafelet of each plasmalemma.

2) dsg and dsc, desmocollin and desmoglein dont really connect in their N terminals as pictured here….  but seem (if one examines the electron microscopy) to be staggered. Even the staggered relationships between cell 1 and cell 2 in their own micrograph have the densities staggered (or alternating).

3) I havn’t seen any reports that say the desmocollin and desmoglein run as a single unit together in the intercellular space which is shown in this diagram.

4) given that desmocollin and desmoglein have a single-pass transmembrane domain and an extended portion into the intracellular space (in the outer and possible the inner dense plaques) it would have been nice to see a little bit of that passing through the red and orange twists that they have labeled pkp and pg = plakophilin and plakoglobin.

5) Since desmoglein does extend into the intracellular space and in this diagram is colored blue, it might have been a better idea to color the dp = desmoplakin some other color, since the continuity of those two molecules as the same color is confusing.

6) it is not tough to make things in relative ratios — a kind of internal scale and when something like the plasmalemma in the diagram is so tiny compared to the other drawn blobs, somehow it speaks to “inattentiveness” or lack of real perception than the need to fit a publication dimension or pixel level.  AND, it provides bad data to those who look at the diagram and learn visually.

7) it is actually kind of cute, the common copying mistake that diagrammers make when they try to depict something that someone else has committed an error on.  This particular error is soooo obnoxious that it makes me wonder if the scientists who requested the diagram know any more than the diagrammers who diagrammed the diagram.  The intermediate filaments in their own micrograph (left part of the image) are not these hairpin wired things darting in to connect with the desmoplakin molecules but they are seen as dots, or pretty much cross sections with a few that look like arcs.  Their diagram shows hairpin curved lines (purple) as intermediate filaments as they connect with desmoplakin but shows NONE of the intermediate filaments in cross section, ha ha, but 100% as arcs… this is just an error.

8) the periodicity of the outer dense plaque proteins (that would be a combination of desmoglein, desmocollin, plakophilin and plakoglobin and whatever portion od desmoplakin sticks in to connect as well is not defined in their electron micrograph. I do think one exists, and it has been reported to be the same dimensions (same number of nm between densities), but certainly can’t be borne out in their own TEM.

9) the central dense line (extracellular) where desmocollin and desmoglein attach, in the diagram they present would surely show a lucent dot, where they have their molecules coming together…  NOT as is typically seen, a definite density, and regular periodicity.

10) The desmoplakin twisted glue lines has two prominent areas at the N and C terminals which some have depicted as

So this if fun for me, again, not to aggravate anyone, but to identify which diagrams can be used to educate, and which need to be pitched as fake news.

“The cytoplasmic surface of intercellular junctions is a complex network of molecular interactions that link the extracellular region of the desmosomal cadherins with the cytoskeletal intermediate filaments. Although 3D structures of the major plaque components are known, the overall architecture remains unknown.” Al Amoudi et al, PNAS April 2011.
Theirs is the best diagram of the desmosome that I have found to date.
1) obvious lattice structure (periodicity)
2) intracellular lattice pretty much matches the periodicity of the extracellular lattice

“No intracellular molecular model for Dsc or Dsg “The structures of the cytoplasmic domains of desmoglein (Dsg) and desmocollin (Dsc) are not available. However, an alignment of their sequences with those of E-cadherin shows that most of the observed E-cadherin/β -catenin interactions are likely to be conserved in desmosomal cadherin/plakoglobin complexes. Therefore, we modeled plakoglobin-binding residues of desmosomal cadherins on the E-cadherin/β-catenin structure.” “Most of the cytoplasmic domain of Dscs (approximately 150 among approximately 200 aa) is modeled based on the E-cadherin/ β-catenin structure. The cytoplasmic region of Dsg is significantly larger and cannot be accounted for in our model. We speculate that the remaining region of the cytoplasmic domains of Dsg could span the region between the ODP and IDP, as proposed from sequence analysis (23), and thus it is not shown in our map of the ODP. According to Al Amoudi. Giving all credit to them, here is their diagram…. which needs some work, i know they know.  Firstly they have made the intracellular and transmembrane portions of the moleules (Dsc and Dsg) the same, which they say are not the same. Secondly… i dont think the figure 8 shape is what is seen in TEMs, sometimes yes, but mostly no… so the orientation of these molecules needs some adjusting.  Thirdly…  the inner and outer intracytoplasmic dense plaques are not the same relative sizes… but their molecules here are the same size…  and for all my observing of models of

I tried to figure out the transmission electron micrographs of an article on desmoplakin and intermediate filament attachment in cultured cells by Bornslaeger et al, The Journal of Cell Biology, Volume 134, Number 4, August 1996 985-1001 and really found the descriptions and TEMs difficult to interpret. Not diminishing their efforts, the micrograph B is clearly not the same magnification as the others which were all pinned under their micron marker of 100nm. Secondly they point to some strange thing as the IF in their first and second images (not shown in what i cropped as the left (A and B) images when there are IF that could have been pointed out just above the inner dense plaque. The IFs which are not connected to the inner dense plaque (they attribute to the loss of functional desmoplakin IF connections) are easy to see in E and E  (both from their figure E, i cut and pasted two portions from their figure). I guess they accomplished what they set out to acomplish… the diminution of the inner plaque and loss of densities beside-with-attached-to the adjacent IFs. I sure didnt enjoy reading this overly acronymish publication (haha).  Desmoplakin is an abundant molecule in desmosome formation, and accounts for some serious electron density  in the inner plaque region.  It is interesting, too, that the IFs are parallel to the plasmalemma, regardless of the blocking of functional desmoplakin, this orientation did not change from what is typically seen.